POS0322 CLINICAL DISEASE ACTIVITY INDEX REMISSION IN RHEUMATOID ARTHRITIS AT 6 MONTHS IS ASSOCIATED WITH HIGHER FREQUENCY OF TRANSITIONAL B CELLS AT DIAGNOSIS
Authors: S. Mcgrath, B. Sundbeck, C. Jonsson, K. Thorarinsdottir, A. Camponeschi, M. Gatto, A. K. H. Ekwall, R. Van Vollenhoven, A. Rudin, I. L. Mårtensson, I. Gjertsson
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Early intervention and implementation of effective treatment is a significant predictor of positive long-term prognosis for rheumatoid arthritis (RA). However, despite major advances in treatment options there are currently no biomarkers to clinically guide treatment selection or to identify individuals who do not respond fully to first line therapy. B cells are known to contribute to RA pathogenesis as exemplified by the success of B cell depleting treatments. It is well known that there are changes in the circulating B cell compartment in both new onset and established RA that include reduced memory B cells and increased naïve and transitional B cells. Among transitional B cells there is a subpopulation described as regulatory B cells (Bregs) that is characterised by markers such as high levels of CD24/CD38, and CD1d as well as PDL1 and production of IL-10. To investigate the predictive potential of the B cell compartment for disease outcome, the different B cell populations must be further divided into specific subset and studied in well characterised cohort followed over time. <h3>Objectives</h3> To identify a B cell subset(s) at clinical onset that predict clinical disease activity index (CDAI) remission 6 months after start of treatment. <h3>Methods</h3> Flow cytometry analysis of peripheral blood B cell subsets was conducted on untreated, early RA patients (ueRA; according to ACR/EULAR 1987/2010 criteria; n=71) and sex matched healthy controls (n=24). PBMCs were stained for the following markers: CD19, CD21, CD27, IgD, CD24, CD38, PD1, PDL1. Patients were then treated with methotrexate and randomised to combination with a) prednisolone; b) certolizumab; c) tocilizumab; or d) abatacept. Patients were grouped based on disease remission status at 6 months (remission n=29; no remission n=42) as defined by a clinical disease activity index (CDAI) &lt;2.8. The predictive value of these population frequencies for remission detection was modelled with receiver operating characteristic (ROC) analysis. Peripheral blood from a second ueRA cohort (n=32) and additional healthy donors (n=11) were analysed by flow cytometry including CD1d, PD1 and PDL1. <h3>Results</h3> Relative to patients who reached CDAI remission, individuals who did not respond to this extent to first line therapy at 6 months had significantly reduced frequencies of transitional (CD19<sup>+</sup> CD24<sup>++</sup> CD38<sup>++</sup>), and PD1<sup>+</sup> B cells (CD19<sup>+</sup> PD1<sup>+</sup> CD21<sup>–</sup>) at diagnosis (Figure 1), which inversely correlated with CDAI at 6 months (r=–0.355, p=0.002; and r=–0.245, p=0.039 respectively). The predictive value of these subset frequencies for remission was modelled with ROC analysis. Both transitional and PD1<sup>+</sup> B cell frequencies had significant predictive capabilities and an AUC of 0.67 and 0.7 respectively (Figure 1). Follow-up analysis in the second RA cohort showed that CD1d<sup>+</sup> transitional B cells in ueRA patients (median 14.75%; range 9.4-23.4%; n=32) were significantly increased (p&lt;0.0001, Mann-Whitney) relative to healthy donors (median 8.9%; range 4.4-12.9%; n=11). <h3>Conclusion</h3> A reduced frequency of transitional and PD1<sup>+</sup> B cells at diagnosis in ueRA patients was associated with failure to reach CDAI remission within 6 months of treatment. As transitional B cells in ueRA patients express markers closely linked to Bregs, we speculate that the lower transitional B cell frequencies we observed at diagnosis may indicate fewer circulating Bregs and thereby worse conditions for endogenous disease control. Thus, monitoring of transitional B cell frequencies at the point of RA diagnosis may aid in the identification of patients who are less likely to reach remission at 6 months and therefore subjected to additional clinical surveillance. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.